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1.
Int J Biol Sci ; 20(10): 3972-3985, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39113693

RESUMEN

Histone methyltransferase KMT2D is one of the most frequently mutated genes in diffuse large B-cell lymphoma (DLBCL) and has been identified as an important pathogenic factor and prognostic marker. However, the biological relevance of KMT2D mutations on tumor microenvironment remains to be determined. KMT2D mutations were assessed by whole-genome/exome sequencing (WGS/WES) in 334 patients and by targeted sequencing in 427 patients with newly diagnosed DLBCL. Among all 761 DLBCL patients, somatic mutations in KMT2D were observed in 143 (18.79%) patients and significantly associated with advanced Ann Arbor stage and MYC expression ≥ 40%, as well as inferior progression-free survival and overall survival. In B-lymphoma cells, the mutation or knockdown of KMT2D inhibited methylation of lysine 4 on histone H3 (H3K4), downregulated FBXW7 expression, activated NOTCH signaling pathway and downstream MYC/TGF-ß1, resulting in alterations of tumor-induced regulatory T cell trafficking. In B-lymphoma murine models established with subcutaneous injection of SU-DHL-4 cells, xenografted tumors bearing KMT2D mutation presented lower H3K4 methylation, higher regulatory T cell recruitment, thereby provoking rapid tumor growth compared with wild-type KMT2D via FBXW7-NOTCH-MYC/TGF-ß1 axis.


Asunto(s)
Proteína 7 que Contiene Repeticiones F-Box-WD , Linfoma de Células B Grandes Difuso , Mutación , Proteínas Proto-Oncogénicas c-myc , Linfocitos T Reguladores , Humanos , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Animales , Ratones , Femenino , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Masculino , Linfocitos T Reguladores/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Receptores Notch/metabolismo , Persona de Mediana Edad , Línea Celular Tumoral , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Transducción de Señal , Adulto , Progresión de la Enfermedad , Anciano
2.
Heliyon ; 10(15): e35053, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39157327

RESUMEN

Background: This study compared the efficacy of oropharyngeal airways (OA) and nasopharyngeal airways (NA) in maintaining oxygenation during painless fiberoptic bronchoscopy (PFB) in patients sedated with remimazolam besylate. Methods: Two hundred and fifty-two patients were randomized to the OA or NA group. Remimazolam besylate was used for anesthesia induction and maintenance in both groups. We measured and recorded several physiological parameters, including mean arterial pressure, heart rate and oxygen saturation (SpO2), at various time points: before anesthesia (T1), after anesthesia induction (T2), immediately after the bronchoscope reached the trachea (T3), during the procedure (T4), and 5 min after transfer to the post-anesthesia care unit (T5). The incidence and frequency of hypoxemia, minimum SpO2 during the procedure and patient awakening time after flumazenil administration were also recorded. Additionally, the relationship between minimum SpO2 and body mass index (BMI) was investigated. Results: Patients in the NA group experienced a higher incidence of hypoxemia compared to the OA group. Patients in the OA group maintained higher SpO2 levels at T3 and had a higher minimum SpO2 during the procedure than the NA group. Furthermore, a significant negative correlation was observed between minimum SpO2 and BMI. Following flumazenil anesthesia reversal, nearly 97 % of patients awakened within 1 min. Conclusions: This study suggests that OA may provide a better safety profile than NA by preserving respiratory function during PFB.

3.
BMC Oral Health ; 24(1): 805, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39014355

RESUMEN

OBJECTIVES: This study pursued two main purposes. The first aim was to expound on the microscopic factors of radiation-related caries (RRC). Further, it aimed to compare the remineralization effect of different remineralizing agents on demineralized teeth after radiotherapy. METHODS: The enamel and dentin samples of bovine teeth were irradiated with different doses of radiation. After analysis of scanning electron microscope (SEM), X-Ray diffraction (XRD), and energy dispersive spectrometer (EDS), the samples irradiated with 50 Gy radiation were selected and divided into the demineralization group, the double distilled water (DDW) group, the Sodium fluoride (NaF) group, the Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) group, the NaF + CPP-ACP group, and the Titanium tetrafluoride (TiF4) group. After demineralization, remineralizing agents treatment, and remineralization, the samples were evaluated using SEM, atomic force microscope (AFM), EDS, and transverse microradiography (TMR). RESULTS: A radiation dose of 30 Gy was sufficient to cause damage to the dentinal tubules, but 70 Gy radiation had little effect on the microstructure of enamel. Additionally, the NaF + CPP-ACP group and the TiF4 group significantly promoted deposit formation, decreased surface roughness, and reduced mineral loss and lesion depth of demineralized enamel and dentin samples after radiation. CONCLUSIONS: Radiation causes more significant damage to dentin compared to enamel. NaF + CPP-ACP and TiF4 had a promising ability to promote remineralization of irradiated dental hard tissues. ADVANCES IN KNOWLEDGE: This in vitro study contributes to determining a safer radiation dose range for teeth and identifying the most effective remineralization approach for RRC.


Asunto(s)
Caseínas , Esmalte Dental , Dentina , Microscopía Electrónica de Rastreo , Fluoruro de Sodio , Remineralización Dental , Animales , Bovinos , Remineralización Dental/métodos , Caseínas/uso terapéutico , Dentina/efectos de la radiación , Dentina/efectos de los fármacos , Fluoruro de Sodio/uso terapéutico , Esmalte Dental/efectos de la radiación , Esmalte Dental/efectos de los fármacos , Difracción de Rayos X , Titanio , Cariostáticos/uso terapéutico , Microrradiografía , Microscopía de Fuerza Atómica , Fluoruros/uso terapéutico , Espectrometría por Rayos X , Caries Dental/etiología , Desmineralización Dental/etiología , Técnicas In Vitro
4.
Adv Mater ; 36(30): e2313059, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38871341

RESUMEN

Artificial moiré superlattices created by stacking 2D crystals have emerged as a powerful platform with unprecedented material-engineering capabilities. While moiré superlattices are reported to host a number of novel quantum states, their potential for spintronic applications remains largely unexplored. Here, the effective manipulation of spin-orbit torque (SOT) is demonstrated using moiré superlattices in ferromagnetic devices comprised of twisted WS2/WS2 homobilayer (t-WS2) and CoFe/Pt thin films by altering twisting angle (θ) and gate voltage. Notably, a substantial enhancement of up to 44.5% is observed in SOT conductivity at θ ≈ 8.3°. Furthermore, compared to the WS2 monolayer and untwisted WS2/WS2 bilayers, the moiré superlattices in t-WS2 enable a greater gate-voltage tunability of SOT conductivity. These results are related to the generation of the interfacial moiré magnetic field by the real-space Berry phase in moiré superlattices, which modulates the absorption of the spin-Hall current arising from Pt through the magnetic proximity effect. This study highlights the moiré physics as a new building block for designing enhanced spintronic devices.

5.
Neuroimage ; 297: 120707, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38942102

RESUMEN

Under resource distribution context, individuals have a strong aversion to unfair treatment not only toward themselves but also toward others. However, there is no clear consensus regarding the commonality and distinction between these two types of unfairness. Moreover, many neuroimaging studies have investigated how people evaluate and respond to unfairness in the abovementioned two contexts, but the consistency of the results remains to be investigated. To resolve these two issues, we sought to summarize existing findings regarding unfairness to self and others and to further elucidate the neural underpinnings related to distinguishing evaluation and response processes through meta-analyses of previous neuroimaging studies. Our results indicated that both types of unfairness consistently activate the affective and conflict-related anterior insula (AI) and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA), but the activations related to unfairness to self appeared stronger than those related to others, suggesting that individuals had negative reactions to both unfairness and a greater aversive response toward unfairness to self. During the evaluation process, unfairness to self activated the bilateral AI, dACC, and right dorsolateral prefrontal cortex (DLPFC), regions associated with unfairness aversion, conflict, and cognitive control, indicating reactive, emotional and automatic responses. In contrast, unfairness to others activated areas associated with theory of mind, the inferior parietal lobule and temporoparietal junction (IPL-TPJ), suggesting that making rational judgments from the perspective of others was needed. During the response, unfairness to self activated the affective-related left AI and striatum, whereas unfairness to others activated cognitive control areas, the left DLPFC and the thalamus. This indicated that the former maintained the traits of automaticity and emotionality, whereas the latter necessitated cognitive control. These findings provide a fine-grained description of the common and distinct neurocognitive mechanisms underlying unfairness to self and unfairness to others. Overall, this study not only validates the inequity aversion model but also provides direct evidence of neural mechanisms for neurobiological models of fairness.


Asunto(s)
Mapeo Encefálico , Imagen por Resonancia Magnética , Humanos , Mapeo Encefálico/métodos , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Emociones/fisiología
7.
Am J Orthod Dentofacial Orthop ; 166(1): 81-91, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38661622

RESUMEN

INTRODUCTION: This study aimed to perform a bibliometric analysis examining contributing countries and collaborative networks, authors and collaborative relationships, the performance of the institutions, and cocited journals and references in 3 major orthodontic journals (American Journal of Orthodontics and Dentofacial Orthopedics, European Journal of Orthodontics, and Angle Orthodontist) over two 10-year periods (2002-2011 and 2012-2021). METHODS: In this study, 4432 publications in the first decade and 4012 publications in the second decade were quantitatively analyzed and visualized using visualization software such as VOSviewer (Leiden University, Leiden, Netherlands), CiteSpace (Drexel University, Philadelphia, Pa), and Scimago Graphica (SCImago Lab, Spain). RESULTS: Institutions in the United States had the highest number of publications through the 2 decades, whereas Brazil, South Korea, and China achieved significant improvements in performance in the second decade compared with the first. Closer collaborative networks among scholars were revealed in the second decade. The cocitation analysis of the journals showed that highly cited journals included more professional orthodontic journals in the second decade than in the first decade. CONCLUSIONS: Bibliometric analysis of publications in 3 major orthodontic journals over two 10-year periods revealed a trend of diversification in countries and institutions participating in publishing, international collaborations, and collaboration networks among authors in the field of orthodontics during the 2 decades.


Asunto(s)
Bibliometría , Ortodoncia , Publicaciones Periódicas como Asunto , Ortodoncia/estadística & datos numéricos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Humanos , Edición/estadística & datos numéricos , Factores de Tiempo
8.
Clin Immunol ; 263: 110206, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38599263

RESUMEN

Patients suffering from sepsis-induced acute lung injury (ALI) exhibit a high mortality rate, and their prognosis is closely associated with infiltration of neutrophils into the lungs. In this study, we found a significant elevation of CD64+ neutrophils, which highly expressed p75 neurotrophin receptor (p75NTR) in peripheral blood of mice and patients with sepsis-induced ALI. p75NTR+CD64+ neutrophils were also abundantly expressed in the lung of ALI mice induced by lipopolysaccharide. Conditional knock-out of the myeloid lineage's p75NTR gene improved the survival rates, attenuated lung tissue inflammation, reduced neutrophil infiltration and enhanced the phagocytic functions of CD64+ neutrophils. In vitro, p75NTR+CD64+ neutrophils exhibited an upregulation and compromised phagocytic activity in blood samples of ALI patients. Blocking p75NTR activity by soluble p75NTR extracellular domain peptide (p75ECD-Fc) boosted CD64+ neutrophils phagocytic activity and reduced inflammatory cytokine production via regulation of the NF-κB activity. The findings strongly indicate that p75NTR+CD64+ neutrophils are a novel pathogenic neutrophil subpopulation promoting sepsis-induced ALI.


Asunto(s)
Lesión Pulmonar Aguda , Ratones Endogámicos C57BL , Neutrófilos , Fagocitosis , Receptores de IgG , Receptores de Factor de Crecimiento Nervioso , Sepsis , Animales , Lesión Pulmonar Aguda/inmunología , Lesión Pulmonar Aguda/etiología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Sepsis/inmunología , Sepsis/complicaciones , Humanos , Receptores de IgG/metabolismo , Receptores de IgG/genética , Receptores de IgG/inmunología , Ratones , Masculino , Fagocitosis/inmunología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Receptores de Factor de Crecimiento Nervioso/genética , Receptores de Factor de Crecimiento Nervioso/inmunología , Ratones Noqueados , Lipopolisacáridos , Citocinas/metabolismo , Citocinas/inmunología , Pulmón/inmunología , Pulmón/patología , Femenino , FN-kappa B/metabolismo , FN-kappa B/inmunología , Proteínas del Tejido Nervioso
9.
Transl Psychiatry ; 14(1): 151, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38504095

RESUMEN

Integrating CYP2D6 genotyping and therapeutic drug monitoring (TDM) is crucial for guiding individualized atomoxetine therapy in children with attention-deficit/hyperactivity disorder (ADHD). The aim of this retrospective study was (1) to investigate the link between the efficacy and tolerability of atomoxetine in children with ADHD and plasma atomoxetine concentrations based on their CYP2D6 genotypes; (2) to offer TDM reference range recommendations for atomoxetine based on the CYP2D6 genotypes of children receiving different dosage regimens. This retrospective study covered children and adolescents with ADHD between the ages of 6 and <18, who visited the psychological and behavioral clinic of Children's Hospital of Nanjing Medical University from June 1, 2021, to January 31, 2023. The demographic information and laboratory examination data, including CYP2D6 genotype tests and routine TDM of atomoxetine were obtained from the hospital information system. We used univariate analysis, Mann-Whitney U nonparametric test, Kruskal-Wallis test, and the receiver operating characteristic (ROC) curve to investigate outcomes of interest. 515 plasma atomoxetine concentrations of 385 children (325 boys and 60 girls) with ADHD between 6 and 16 years of age were included for statistical analysis in this study. Based on genotyping results, >60% of enrolled children belonged to the CYP2D6 extensive metabolizer (EM), while <40% fell into the intermediate metabolizer (IM). CYP2D6 IMs exhibited higher dose-corrected plasma atomoxetine concentrations by 1.4-2.2 folds than those CYP2D6 EMs. Moreover, CYP2D6 IMs exhibited a higher response rate compare to EMs (93.55% vs 85.71%, P = 0.0132), with higher peak plasma atomoxetine concentrations by 1.67 times than those of EMs. Further ROC analysis revealed that individuals under once daily in the morning (q.m.) dosing regimen exhibited a more effective response to atomoxetine when their levels were ≥ 268 ng/mL (AUC = 0.710, P < 0.001). In addition, CYP2D6 IMs receiving q.m. dosing of atomoxetine were more likely to experience adverse reactions in the central nervous system and gastrointestinal system when plasma atomoxetine concentrations reach 465 and 509 ng/mL, respectively. The findings in this study provided promising treatment strategy for Chinese children with ADHD based on their CYP2D6 genotypes and plasma atomoxetine concentration monitoring. A peak plasma atomoxetine concentration higher than 268 ng/mL might be requisite for q.m. dosing. Assuredly, to validate and reinforce these initial findings, it is necessary to collect further data in controlled studies with a larger sample size.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Adolescente , Niño , Femenino , Humanos , Masculino , Inhibidores de Captación Adrenérgica/efectos adversos , Clorhidrato de Atomoxetina/efectos adversos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/genética , Citocromo P-450 CYP2D6/genética , Monitoreo de Drogas , Genotipo , Propilaminas/efectos adversos , Estudios Retrospectivos , Lactante , Preescolar
10.
Blood Adv ; 8(7): 1587-1599, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38170757

RESUMEN

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of lymphoma with clinical and biological heterogeneity. The International Prognostic Index (IPI) shows great prognostic capability in the era of rituximab, but the biological signatures of IPI remain to be discovered. In this study, we analyzed the clinical data in a large cohort of 2592 patients with newly diagnosed DLBCL. Among them, 1233 underwent DNA sequencing for oncogenic mutations, and 487 patients underwent RNA sequencing for lymphoma microenvironment (LME) alterations. Based on IPI scores, patients were categorized into 4 distinct groups, with 5-year overall survival of 41.6%, 55.3%, 71.7%, and 89.7%, respectively. MCD-like subtype was associated with age of >60 years, multiple extranodal involvement, elevated serum lactate dehydrogenase (LDH), and IPI scores ranging from 2 to 5, whereas ST2-like subtype showed an opposite trend. Patients with EZB-like MYC+ and TP53Mut subtypes exhibited poor clinical outcome independent of the IPI; integrating TP53Mut into IPI could better distinguish patients with dismal survival. The EZB-like MYC-, BN2-like, N1-like, and MCD-like subtypes had inferior prognosis in patients with IPI scores of ≥2, indicating necessity for enhanced treatment. Regarding LME categories, the germinal center-like LME was more prevalent in patients with normal LDH and IPI scores of 0 to 1. The mesenchymal LME served as an independent protective factor, whereas the germinal center-like, inflammatory, and depleted LME categories correlated with inferior prognosis for IPI scores of 2 to 5. In summary, our work explored the biological signatures of IPI, thus providing useful rationale for future optimization of the IPI-based treatment strategies with multi-omics information in DLBCL.


Asunto(s)
Linfoma de Células B Grandes Difuso , Humanos , Persona de Mediana Edad , Pronóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/uso terapéutico , Centro Germinal/patología , Microambiente Tumoral
12.
Am J Orthod Dentofacial Orthop ; 165(4): 471-487, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38276931

RESUMEN

INTRODUCTION: In many evidence-based approaches to orthodontic research, randomized controlled trials (RCTs) represent authoritative evidence to identify rational therapeutics. This study aimed to perform mappings of bibliometric networks on orthodontic RCTs and summarize visual characteristics between 1991 and 2022. METHODS: The articles were retrieved from the Web of Science Core Collection in October 2022 without an initial time limit. Only orthodontic RCTs were eligible. Some bibliometric tools (HistCite, VOSviewer, SCImago Graphica, and CiteSpace) were applied for visualized analysis. Data such as geography, productive institutions, hot articles, journals, authors, references, and keywords were extracted and summarized for analysis. RESULTS: A total of 1122 orthodontic RCTs were searched. A total of 3841 authors from 1157 institutions in 65 countries published orthodontic RCTs. The United States (149) was the most prolific country, and the University of Sao Paulo (35) was the most productive institution. The American Journal of Orthodontics and Dentofacial Orthopedics (206) was the most popular journal for scholars. The visualization results of keyword co-occurrence identified 5 clusters: (1) tooth movement and auxiliary measures, (2) appliances and oral health, (3) orthodontic discomfort and symptomatic therapy, (4) periodontal disease in orthodontics and health maintenance, and (5) retention and relapse. CONCLUSIONS: Over the past 31 years, publications and citations on orthodontic RCTs from the Web of Science Core Collection have increased notably across many countries, authors, and institutions. Recently, there has been a significant increase in the attention to orthodontic RCTs that focus on accelerating tooth movement.


Asunto(s)
Atención Odontológica , Ortopedia , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Salud Bucal , Bibliometría
13.
J Clin Endocrinol Metab ; 109(6): 1540-1549, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38124275

RESUMEN

CONTEXT: There is limited data on the clinical significance of metabolic hyperferritinemia (MHF) based on the most recent consensus. OBJECTIVE: We aimed to validate the clinical outcomes of MHF in the general population and patients with biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: The NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males]-550 ng/mL; grade 2: 550-1000 ng/mL; grade 3: >1000 ng/mL). The clinical outcomes, including all-cause death, comorbidities, and liver histology, were compared between non-MHF and MHF in adjusted models. RESULTS: In NHANES, compared with non-MHF with MD, MHF was related to higher risks of advanced fibrosis (P = .036), elevated albumin-creatinine ratio (UACR, P = .001), and sarcopenia (P = .013). Although the association between all grades of MHF and mortality was insignificant (P = .122), grades 2/3 was associated with increased mortality (P = .029). When comparing with non-MHF without MD, the harmful effects of MHF were more significant in mortality (P < .001), elevated UACR (P < .001), cardiovascular disease (P = .028), and sarcopenia (P < .001). In the PERSONS cohort, MHF was associated with more advanced grades of steatosis (P < .001), lobular inflammation (P < .001), advanced fibrosis (P = .017), and more severe hepatocellular iron deposition (P < .001). CONCLUSION: Both in the general population and in at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes.


Asunto(s)
Ferritinas , Hiperferritinemia , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios de Cohortes , Hiperferritinemia/sangre , Hiperferritinemia/diagnóstico , Ferritinas/sangre , Consenso , Encuestas Nutricionales , Anciano , Pronóstico
14.
Cancer Cell ; 41(10): 1705-1716.e5, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37774697

RESUMEN

We report the results of GUIDANCE-01 (NCT04025593), a randomized, phase II trial of R-CHOP alone or combined with targeted agents (R-CHOP-X) guided by genetic subtyping of newly diagnosed, intermediate-risk, or high-risk diffuse large B cell lymphoma (DLBCL). A total of 128 patients were randomized 1:1 to receive R-CHOP-X or R-CHOP. The study achieved the primary endpoint, showing significantly higher complete response rate with R-CHOP-X than R-CHOP (88% vs. 66%, p = 0.003), with overall response rate of 92% vs. 73% (p = 0.005). Two-year progression-free survival rates were 88% vs. 63% (p < 0.001), and 2-year overall survival rates were 94% vs. 77% (p = 0.001). Meanwhile, post hoc RNA-sequencing validated our simplified genetic subtyping algorithm and previously established lymphoma microenvironment subtypes. Our findings highlight the efficacy and safety of R-CHOP-X, a mechanism-based tailored therapy, which dually targeted genetic and microenvironmental alterations in patients with newly diagnosed DLBCL.

15.
Cancer Commun (Lond) ; 43(8): 896-908, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37403255

RESUMEN

BACKGROUND: The current standard of care for non-bulky diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) of 0 is four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) but whether the same efficacy can be achieved with reduced chemotherapy regimen of four cycles for non-bulky DLBCL patients with an IPI of 1 remains unclear. This study compared four cycles versus six cycles of chemotherapy in non-bulky low-risk DLBCL patients with negative interim positron emission tomography with computed tomography (PET-CT, Deauville 1-3), irrespective of age and other IPI risk factors (IPI 0-1). METHODS: This was an open-label, randomized, phase III, non-inferiority trial. Patients aged 14-75 years with newly diagnosed low-risk DLBCL, according to IPI, achieving PET-CT confirmed complete response (CR) after four cycles of R-CHOP were randomized (1:1) between four cycles of rituximab (4R-CHOP+4R arm) or two cycles of R-CHOP plus two cycles of rituximab (6R-CHOP+2R arm). The primary endpoint was 2-year progression-free survival (PFS), conducted in the intention-to-treat population. Safety was assessed in patients with at least one cycle of assigned treatment. The non-inferiority margin was -8%. RESULTS: A total of 287 patients were included in the intention-to-treat analysis, the median follow-up was 47.3 months, and the 2-year PFS rate was 95% (95% confidence interval [CI], 92% to 99%) and 94% (95% CI, 91% to 98%) for the 4R-CHOP+4R and 6R-CHOP+2R arm. The absolute difference in 2-year PFS between the two arms was 1% (95% CI, -5% to 7%), supporting the non-inferiority of 4R-CHOP+4R. Grade 3-4 neutropenia was lower in the last four cycles of rituximab alone in the 4R-CHOP+4R arm (16.7% versus 76.9%), with decreased risk of febrile neutropenia (0.0% versus 8.4%) and infection (2.1% versus 14.0%). CONCLUSIONS: For newly diagnosed low-risk DLBCL patients, interim PET-CT after four cycles of R-CHOP was effective in identifying patients with Deauville 1-3 who would have a good response and Deauville 4-5 patients who might have high-risk biological features or develop resistance. Reducing the standard six cycles to four cycles of chemotherapy had comparable clinical efficacy and fewer adverse events in low-risk, non-bulky DLBCL with interim PET-CT confirmed CR.


Asunto(s)
Linfoma de Células B Grandes Difuso , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Rituximab , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Supervivencia sin Enfermedad , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Vincristina/efectos adversos , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Prednisona/efectos adversos , Tomografía de Emisión de Positrones/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
16.
ESC Heart Fail ; 10(4): 2479-2486, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37277924

RESUMEN

AIMS: This study aimed to identify a novel splicing-altering LAMP2 variant associated with Danon disease. METHODS AND RESULTS: To identify the potential genetic mutation in a Chinese pedigree, whole-exome sequencing was conducted in the proband, and Sanger sequencing was performed on the proband's parents. To verify the impact of the splice-site variant, a minigene splicing assay was applied. The AlphaFold2 analysis was used to analyse the mutant protein structure. A splice-site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified as a potential pathogenic variant. The minigene splicing revealed that this variant causes exon 6 to be skipped, resulting in a truncated protein. The AlphaFold2 analysis showed that the mutation caused a protein twist direction change, leading to conformational abnormality. CONCLUSIONS: A novel splice-site variant (NM_013995.2:c.864+5G>A) located at intron 6 of the LAMP2 gene was identified. This discovery may enlarge the LAMP2 variant spectrum, promote accurate genetic counselling, and contribute to the diagnosis of Danon disease.


Asunto(s)
Enfermedad por Depósito de Glucógeno de Tipo IIb , Empalme del ARN , Humanos , Pueblos del Este de Asia , Enfermedad por Depósito de Glucógeno de Tipo IIb/genética , Enfermedad por Depósito de Glucógeno de Tipo IIb/diagnóstico , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Mutación , Linaje
17.
Int J Soc Robot ; : 1-16, 2023 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-37359433

RESUMEN

To enhance human-robot social interaction, it is essential for robots to process multiple social cues in a complex real-world environment. However, incongruency of input information across modalities is inevitable and could be challenging for robots to process. To tackle this challenge, our study adopted the neurorobotic paradigm of crossmodal conflict resolution to make a robot express human-like social attention. A behavioural experiment was conducted on 37 participants for the human study. We designed a round-table meeting scenario with three animated avatars to improve ecological validity. Each avatar wore a medical mask to obscure the facial cues of the nose, mouth, and jaw. The central avatar shifted its eye gaze while the peripheral avatars generated sound. Gaze direction and sound locations were either spatially congruent or incongruent. We observed that the central avatar's dynamic gaze could trigger crossmodal social attention responses. In particular, human performance was better under the congruent audio-visual condition than the incongruent condition. Our saliency prediction model was trained to detect social cues, predict audio-visual saliency, and attend selectively for the robot study. After mounting the trained model on the iCub, the robot was exposed to laboratory conditions similar to the human experiment. While the human performance was overall superior, our trained model demonstrated that it could replicate attention responses similar to humans.

19.
China CDC Wkly ; 5(17): 369-373, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37197449

RESUMEN

What is already known about this topic?: A considerable percentage of the population has received both primary and booster vaccinations, which could potentially provide protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infections and related symptoms. What is added by this report?: The self-reported infection rate, as determined from an online survey, reached its peak (15.5%) between December 19 and 21, 2022, with an estimated 82.4% of individuals in China being infected as of February 7, 2023. During the epidemic, the effectiveness of booster vaccinations against SARS-CoV-2 Omicron infection was found to be 49.0% within three months of vaccination and 37.9% between 3 and 6 months following vaccination. Furthermore, the vaccine effectiveness of the booster vaccination in relation to symptom prevention varied from 48.7% to 83.2% within three months and from 25.9% to 69.0% between 3 and 6 months post-booster vaccination. What are the implications for public health practice?: The development and production of efficacious vaccines, together with prompt vaccinations or emergency vaccinations, have the potential to mitigate the epidemic's impact and safeguard public health.

20.
Biochem Cell Biol ; 101(5): 456-463, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37192548

RESUMEN

It is critical to find efficient non-invasive prognostic factor for osteosarcoma. In this study, we demonstrated that serum protein of pro-surfactant protein B (pro-SFTPB) may be a potential diagnostic indicator in osteosarcoma. We found that serum pro-SFTPB was highly expressed in osteosarcoma patients and presented good diagnostic value to discern osteosarcoma patients from non-osteosarcoma control subjects. Serum pro-SFTPB was also significantly correlated with advanced clinical stage, distant metastasis, and shorter overall survival. In addition, serum pro-SFTPB was demonstrated to be an independent prognostic factor for osteosarcoma. Overall, our study demonstrated that serum pro-SFTPB may be a useful diagnostic factor for osteosarcoma.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , Biomarcadores de Tumor , Receptores Fc , Osteosarcoma/patología , Tensoactivos , Neoplasias Óseas/patología
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